Optimization of Immunotherapy Treatment for Advanced Melanoma in the Context of the Public Brazilian Health System (OTIMAS)

Inclusion Criteria

• •Patients with malignant melanoma (with confirmed histopathological diagnosis) stages III and IV not amenable to locoregional treatment or curative treatment
• •Measurable disease by RECIST 1.1
• •Eastern Cooperative Oncology Group (ECOG) 0, 1 or 2
• •Up to 1 (one) line of prior treatment with palliative chemotherapy (monotherapy), with documented progression and no residual toxicities greater than grade 1 according to CTCAE
• •Estimated life expectancy greater than 12 weeks
• •Adequate renal function, defined as creatinine clearance estimated by the Cockcroft-Gault equation equal to or greater than 30 mL/min;
• •Adequate liver function, defined as alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels equal to or less than 2.0 times the upper limit of normal and total bilirubin less than 2 times the upper limit of normal;
• •Hemoglobin greater than or equal to 8 g/dL; neutrophil count equal to or greater than 1,000/mm3; platelet count equal to or greater than 100,000/mm3;
• •Ability to understand and adhere to study procedures;
• •Age over 18 years;
• •Absence of active treatment for the underlying disease, with the exception of the use of bisphosphonates;
• •Diagnosis of uveal or mucosal melanoma;
• •Diagnosis of acral melanoma;
• •Leptomeningeal disease
• •Pregnancy; effective contraceptive methods should be recommended to women of childbearing age;
• •Uncontrolled associated disease;
• •Known active hepatitis B and C;
• •HIV with detectable viral load or CD4\<350;
• •Active autoimmune disease with use of immunosuppressive therapy or history of autoimmune disease whose risk of recurrence is considered high by the investigator;
• •More than one line of prior systemic therapy in the context of metastatic or advanced disease or prior use of polychemotherapy;
• •Prior use of anti-PD-1 in the (neo)adjuvant setting;
• •Concomitant active malignant neoplasia;
• •History of malignant neoplasia in the last 5 years, with the exception of squamous cell carcinoma, basal cell carcinoma of the skin, in situ tumors, prostate adenocarcinoma gleason \<=6;
• •Infection with systemic involvement in the last 2 weeks;
• •Use of corticosteroids in a dose equivalent to greater than 10 mg/d of prednisone on a continuous basis.
• •History of solid organ transplantation under immunosuppression.